Copper-deficient mice have higher cardiac norepinephrine turnover.
Norepinephrine metabolism was investigated in 6-wk-old male Swiss albino copper-deficient and copper-supplemented mice. Beginning 4 d after birth of pups, dams were fed a diet low in copper (Cu) (0.4 mg/kg) and offspring were weaned to this diet at 21 d of age. Half the dams and their respective offspring received Cu (20 micrograms/ml) in the drinking water (+Cu) and served as controls. Unsupplemented offspring (-Cu) had lower liver Cu levels, exhibited anemia, and had increased heart weights but normal body weights compared to +Cu mice. Urinary output of norepinephrine and dopamine was higher, whereas output of creatinine and epinephrine was not different in -Cu mice compared to +Cu mice. Both fractional and calculated turnover of norepinephrine following inhibition of tyrosine 3-monooxygenase by alpha-methyl-p-DL-tyrosine methyl ester (alpha-MT) was higher in hearts from -Cu mice than in those from +Cu mice. Hearts and spleens from -Cu mice appeared to have higher tyrosine 3-monooxygenase activity as judged by increasing rates of L-dihydroxyphenylalanine accumulation following injection of m-hydroxybenzylhydrazine (NSD-1015), an inhibitor of aromatic amino acid decarboxylase. Turnover rates of norepinephrine for cerebellum were not different between +Cu and -Cu mice. Loss of norepinephrine from adrenal glands of mice injected with alpha-MT was not observed in the 8-h period studied. The smaller norepinephrine pool observed in organs of -Cu mice may have resulted from lower synthesis due to limiting dopamine-beta-monooxygenase activity and to higher turnover.
Gross
A M
AM
Department of Biochemistry, School of Medicine, University of Minnesota, Duluth 55812.
Prohaska
J R
JR
D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D002395:Catecholamines / Q000652:urine; D002531:Cerebellum / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003300:Copper / Q000172:deficiency*; D005260:Female; D006834:Hydrazines / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism* / Q000652:urine
D002395:Catecholamines; D006834:Hydrazines; D008781:Methyltyrosines; C022260:alpha-methyltyrosine methyl ester; D003300:Copper; C004297:3-hydroxybenzylhydrazine; D009638:Norepinephrine